Electrical signals recorded from the neurons of human patients by intracortical microelectrodes have been used to communicate with computers, control robotic limbs, and recently in a VA study, control the patient's own arm. The signal quality and the length of time that useful signals can be recorded are inconsistent. The consensus view of the community is that the inflammatory response of neural tissue that surrounds the microelectrodes, at least in part, compromises electrode reliability. Several studies have demonstrated the connection between neuroinflammation and microelectrode performance. Inflammation is initiated when inflammatory cells recognize foreign biologics (i.e. damaged/infiltrating proteins and cells). Serum proteins and blood-derived cells invade the central nervous system following microelectrode implantation and aggravate the neuroinflammatory response. Cells and tissue are damaged from the trauma of microelectrode implantation. At the microelectrode surface, accumulation of pro-inflammatory molecules causes neuronal degeneration and increases the permeability of the blood-brain barrier, self-perpetuating the process. We are exploring several antioxidative approaches to improve microelectrode reliability. Our preliminary data indicates antioxidative approaches as a highly promising strategy. Specifically, we have used a variety of antioxidant treatments to demonstrate a reduction in intracortical microelectrode- mediated oxidative stress and preserve neuron viability. Our newest strategy for improving intracortical recording reliability is our biomimetic antioxidative coating. Thus far, we have shown improvements in acute recording on one electrode type. Chronic recording performance and translation to additional electrode types is a priority. Our coating was developed as a platform technology that could be applied to any intracortical microelectrode substrate with simple modifications to the attachment chemistry. Our initial efforts focused on planar silicon substrates for ease of characterization, cost, and their recent popularity in the literature. Preliminary results suggest that our antioxidative-coated microelectrodes reduce the initial inflammatory response, preserve neuron populations adjacent to the electrodes, and improve initial recording quality. However, we have yet to demonstrate that the coatings can be applied to other popular microelectrode types, such as those used in the clinic. We also still need to characterize the long-term effects of our coatings on both neuroinflammation and the reliability of recording performance. The innovation of this proposal is in the application of a platform technology to effectively minimize two of the leading causes of intracortical microelectrode failure: materials damage and biological damage. This study is designed to answer clinically-relevant questions, and has the potential to directly impact ongoing and future clinical trials by the completion of the proposed study.